Racemic(±)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (licarbazepine) is the principal metabolite of the established anti-epileptic drug oxcarbazepine. This compound has been shown to possess valuable pharmacological properties and a particularly high therapeutic index. In the case of oral or rectal administration it has a central depressant action, an anticonvulsive action, which relaxes the central muscular system and inhibits the fighting reaction of the mouse. These properties determined by selected standard tests [R. Domenjoz and W. Theobald, Arch. Int. Pharmacodyn. 120, 450 (1959) and W. Theobald et al., Arzneimittel Forsch. 17, 561 (1967)] characterize the compound as being suitable for the treatment of psychosomatic disturbances, epilepsy, trigeminal neuralgia and cerebral spasticity.
Eslicarbazepine acetate is a prodrug of eslicarbazepine (S-licarbazepine), a third-generation drug belonging to the carbamazepine family and the active metabolite of oxcarbazepine. (S)-(+)-10,11-Dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (eslicarbazepine) is the key intermediate for the synthesis of antiepilectic drug substance eslicarbazepine acetate.

The synthesis and improved anticonvulsant properties of (S)-(−)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-093), and (R)-(+)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide (BIA 2-059) have been described by Benes, J. et al., in U.S. Pat. No. 5,753,646 and J. Med. Chem., 42, 2582-2587 (1999). The key step of the synthesis of compounds BIA 2-093 and BIA 2-059 involves the resolution of racemic 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide into its separate, optically pure enantiomers, (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide and (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide by esterification of racemic 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxyamide with menthoxyacetic acid, separation of the resulting diasteroisomers followed by hydrolysis of the respective optically active menthoxyacetates leads to optically pure enantiomers.
One of the disadvantages of this method is that it can only be utilized for the preparation of only small quantities of each stereoisomer because the necessary optically pure resolving agents, (+) and (−)-menthoxyacetic acid are enormously expensive and are not readily available in sufficient quantities from commercial sources.
U.S. Pat. No. 7,119,197 discloses a method for the preparation of optically pure (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide and (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide by resolution of racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide using an appropriate tartaric acid anhydride.
US2006142566 discloses a method for the enantioselective preparation of the (S) and (R)-enantiomers of 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide by asymmetric reduction of oxcarbazepine. The asymmetric reduction is carried out in the presence of a ruthenium catalyst and a hydride source. A suitable catalyst may be formed from [RuCl2(p-cymene)]2 and (S,S) or (R,R)—N-(4-toluenesulfonyl)-diphenylethylenediamine. US 2006/0142566 also discloses two crystalline Forms A and B of both the enantiomers of 10,11-dihydro-10 hydroxy-5Hdibenz[b,f]azepine-5-carboxamide, obtainable by the new processes and their usage in the production of pharmaceutical preparations.
US2009203902 discloses a process for preparing (S)-(+)- or (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide, by reduction of oxcarbazepine in the presence of a catalyst and a hydride source. The catalyst is prepared from a combination of [RuX2(L)]2 wherein X is chlorine, bromine or iodine, and L is an aryl or aryl-aliphatic ligand with a ligand of following formula, wherein the variables are as defined in US2009203902. The disadvantage of this process is again the use of ruthenium complex as a catalyst.

US 2010173893 discloses a process for preparing eslicarbazepine acetate ((S)-(−)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide) and R-(+)-licarbazepine acetate ((R)-(+)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide) and their derivatives by asymmetric hydrogenation of the corresponding enol acetate or of the corresponding enol ester derivative using a chiral catalyst and a source of hydrogen. The chiral catalyst is selected from Rh(I) complexes having chiral ligands with the following structures.

The major disadvantages of the above mentioned processes is the residual level of ruthenium/rhodium metal, a most undesirable contaminant in the product, which is high and difficult to remove in a dosage form for the human consumption. Furthermore, these catalysts are expensive and therefore their use can not be regarded as industrially viable.
US 2009105472 discloses a process for preparing (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxyamide starting from racemic 5-cyano-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine by (a) phthaloylation, (b) treating with chiral amine (c) separation of the diastereomeric salts of the phthaloyl derivative with (S)-phenylethylamine, (d) generation of half ester followed by hydrolysis to (S)-(+)-5-cyano-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine and (e) hydrolysis of the nitrile group of the latter to amido group, by treatment with peroxy compounds in alkali medium (Scheme I).

Accordingly, for obtaining the optically pure compound, the five steps sequence is carried out, involving more numbers of reagents and solvents, while increasing the time cycle of the entire sequence. Thus, there remains a need for an environment friendly, industrially feasible and economical process for the preparation of (S)-(+)- and (R)-(−)-10-hydroxy-dihydrodibenz[b,f]azepines.
Therefore, a process is required, which avoids expensive menthoxyacetic acid, used in the known process for the preparation of (S)-(+)- and (R)-(−)-10-hydroxy-dihydro dibenz[b,f]azepines. Moreover, a process is required, which does not involve the use of any transition metal (e.g. ruthenium or rhodium catalyst), the most undesirable contaminant in the product, for asymmetric catalytic reduction of corresponding keto analogue. Furthermore, the transition metals (e.g. ruthenium or rhodium catalyst) are expensive and therefore their use can not be regarded as industrially viable.
Pharmaceutical Research, (2008), 25, 530, explains that the ability to deliver the drug to the patient in a safe, efficacious and cost effective way depends largely upon the physicochemical properties of the APIs in the solid state and accordingly one of the challenging tasks in the pharmaceutical industry is to design pharmaceutical materials with specific physiochemical properties. It is known that different solid forms of the same drug may exhibit different properties, including characteristics that have functional implications with respect to their use as drug may have substantial differences in such pharmaceutically important properties as dissolution rates and bioavailability. Likewise, different polymorphs may have different processing properties, such as hygroscopisity, flow ability and the like, which could affect their suitability as active pharmaceuticals for commercial production. Also, it is known in the art that the amorphous forms of APIs generally exhibit the better solubility profile over the corresponding crystalline forms. This is because the lattice energy does not have to be overcome in order to dissolve the solid state structure as in the case for crystalline forms.
Thus, there is a need to develop the novel solid state forms of pharmaceutically active compound, having better physicochemical properties; specially, for the enhancement of the solubility. Also, there is a constant need to have the cost effective and industrial friendly process for the preparation of the solid state form.